OVERALL: SUMMARY ABSTRACT Nephrolithiasis (or commonly known as urinary stone disease) is a benign but severely painful genitourinary disease that is on the rise and is the second most costly urologic condition in the US at over $2 billion per year. The treatment of nephrolithiasis is shifting away from shock wave lithotripsy (SWL) to intracorporeal laser lithotripsy (LL) via ureteroscopy, but the foundational knowledge of laser-stone-tissue interaction and LL technology has not advanced commensurably with its growing use in clinical care. At present, there is a pressing need for a fundamental and comprehensive investigation of the existing LL technologies and the dissimilar mechanisms of action associated with various modes of LL. Such an effort will be timely and crucial to optimize LL for improved patient-oriented outcomes and long-term surgical management of stone disease. Therefore, the overarching goal of this P20 application is to develop a Center for Urological Laser Technologies (CULT) at Duke University that will synergistically combine the expertise in engineering and urology to better understand the dissimilar laser technologies and techniques used clinically for stone management. This center will focus on a Research Project. The center's team will consist of investigators with expertise in urology, biophotonics, heat transfer, computational mechanics, and materials science to address the challenges faced in advancing laser technologies to treat stone disease. The center's Research Project has two Specific Aims focusing on (1) Characterizing comprehensively the optical, thermal, acoustic, and mechanical properties of kidney and artificial stones of different compositions and investigate the dissimilar mechanisms of stone damage produced by various modes of LL; and (2) Performing an in-depth analysis of laser-induced cavitation bubble dynamics in correlation with stone retropulsion and treatment efficiency produced by different LL devices. The center's Administrative Core will provide infrastructure required to manage the scientific oversight of CULT's Research Project studies and oversee the organizational, budgeting, reporting, outreach, communications, and educational goals of the CULT. CULT's EEP will provide a novel training experience in engineering design and entrepreneurship to the next generation of bioengineers in close collaboration with clinicians interested in benign genitourinary research. Synergies and knowledge created by CULT are expected to propel technological innovation and development in LL systems forward, in collaboration with a leading LL manufacturer Dornier MedTech and other medical device companies, benefitting millions of stone patients worldwide.